This project aims at analyzing the cellular and molecular heterogeneity of various types of human prostate carcinoma-associated antigens (PCAA) identified with monoclonal antibodies and at assessing the clinical significance of the PCAA. Several immunization approaches will be used to develop a library of monoclonal antibodies to the various determinants (individual, cross-reacting and framework) of the different types of tumor-associated antigens expressed on human prostate carcinoma cells. The specificity of these antibodies will be assessed by both serological and immunochemical assays with cell lines and surgically removed tissues and with other prostatic cancer markers. Monoclonal antibodies will be used to purify immunologically functional PCAA which will be analyzed for their structural properties with special emphasis on their glycoprotein or glycolipid nature, subunit structure, molecular heterogeneity (identified by the distribution of antigenic determinants recognized by monoclonal antibodies on subpopulations of molecules within each type of PCAA) and the structural basis underlying this heterogeneity. Monoclonal antibodies to distinct determinants on various types of PCAA will be selected to develop specific and sensitive conventional radioimmunoassays and double determinant immunoassays. The assays will be utilized to investigate the shedding of PCAA by cultured prostate carcinoma cells and to measure the level of PCAA in body fluids of prostate cancer patients. Biopsies of malignant lesions from prostatic cancer patients will be phenotyped with a library of monoclonal antibodies to study cellular heterogeneity of PCAA; the results will be correlated with the clinical course of the disease and with patient response to therapy. The results from these studies will aid in the characterization of the molecular basis of malignant transformation of human cells and in the evaluation of the usefulness of monoclonal antibodies in clinical oncology and will contribute to the understanding of host immunity to malignancy.